Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria
Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria
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穿孔素 -2对于实质细胞和吞噬细胞针对病原菌的细胞内防御至关重要。
DOI：
10.7554/elife.06508
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发表时间：
2015-09-24
期刊：
影响因子：
7.7
通讯作者：
Podack, Eckhard R.
中科院分区：
文献类型：
--
作者：
McCormack, Ryan M.;de Armas, Lesley R.;Podack, Eckhard R.
穿孔蛋白-2（MPEG 1）是一种具有广谱抗菌活性的成孔蛋白。穿孔蛋白-2在吞噬细胞中组成型表达，在实质组织形成细胞中诱导型表达。在体外，穿孔蛋白-2防止这些细胞中细菌病原体的细胞内复制和增殖。穿孔蛋白-2基因敲除小鼠无法控制耐甲氧西林金黄色葡萄球菌（MRSA）或鼠伤寒沙门氏菌的全身传播，并分别在表皮或口胃感染后不久死亡。相比之下，穿孔蛋白-2充足的同窝仔清除感染。穿孔蛋白-2是胞质囊泡的跨膜蛋白-来源于多个细胞器-其易位到含有囊泡的细菌并与之融合。随后，穿孔蛋白-2聚合并在细菌表面中与存在于细菌中的穿孔蛋白-2切割产物形成100埃孔的大簇。穿孔蛋白-2也是活性氧和氮物质以及水解酶的杀菌活性所需的。穿孔蛋白-2构成了先天免疫系统的一种新的和明显必需的杀菌效应分子。
Perforin-2 (MPEG1) is a pore-forming, antibacterial protein with broad-spectrum activity. Perforin-2 is expressed constitutively in phagocytes and inducibly in parenchymal, tissue-forming cells. In vitro, Perforin-2 prevents the intracellular replication and proliferation of bacterial pathogens in these cells. Perforin-2 knockout mice are unable to control the systemic dissemination of methicillin-resistant Staphylococcus aureus (MRSA) or Salmonella typhimurium and perish shortly after epicutaneous or orogastric infection respectively. In contrast, Perforin-2-sufficient littermates clear the infection. Perforin-2 is a transmembrane protein of cytosolic vesicles -derived from multiple organelles-that translocate to and fuse with bacterium containing vesicles. Subsequently, Perforin-2 polymerizes and forms large clusters of 100 angstrom pores in the bacterial surface with Perforin-2 cleavage products present in bacteria. Perforin-2 is also required for the bactericidal activity of reactive oxygen and nitrogen species and hydrolytic enzymes. Perforin-2 constitutes a novel and apparently essential bactericidal effector molecule of the innate immune system.